Studies on the teratogenic effects of different oral preparations of caffeine in mice.

Caffeine in doses up to 250 mg/kg per day in drinking water or up to 150 mg/kg per day in sustained release pellets was administered to pregnant mice. Apart from a low incidence of cleft palate, in the 50 mg/kg and 150 mg/kg caffeine pellet groups no gross abnormalities were observed which were attributable to caffeine treatment. The most important effect observed was a reduction in fetal weight. Retarded ossification particularly of the supraoccipital bones was observed in fetuses when caffeine (150 mg/kg) was administered in drinking water but not when the same dose was given as a sustained release pellet. Analysis of caffeine blood level data showed that the total exposure from the pellets was greater than from the drinking water. It would thus appear that the effect on the supraoccipital bones is an indirect one mediated through reduced food and water intake of the dams when caffeine is administered in drinking water.